{
  "abstract": "Estrogen therapy elicits clinical benefit in ~ 30% of patients with endocrine‐resistant estrogen receptor (ER)‐positive breast cancer, but its mechanism of action and strategies to increase efficacy remain unclear. Estrogen therapy can induce ER transcriptional hyperactivation and DNA damage; we postulated that such damage could be exacerbated by epigenetic dysregulation via inhibition of histone deacetylases (HDACi). We evaluated the effects of 17b‐estradiol and HDACi in three types of ER+ breast cancer models: Cells adapted to growth following long‐term estrogen deprivation; cells engineered to overexpress exogenous ER that confers endocrine resistance; mice bearing endocrine‐resistant patient‐derived xenografts. Assay endpoints included apoptosis, growth, DNA damage, histone post‐translational modification, levels of ER‐regulated transcripts and encoded proteins, cell cycle and replication status, and genome‐wide chromatin accessibility, ER binding, and transcriptional profiles. Entinostat treatment increased histone acetylation and chromatin accessibility. Combination treatment with E2 and entinostat inhibited cell growth and induced apoptosis in ER‐overexpressing models. E2 and entinostat induced DNA damage as single agents and in combination. These agents synergized against tumor models, offering HDACi as a strategy to enhance efficacy of estrogen therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular and Systems Biology Dartmouth Geisel School of Medicine Lebanon NH USA",
    "Department of Pharmacology and Toxicology Medical College of Wisconsin Milwaukee WI USA",
    "Department of Epidemiology, Geisel School of Medicine Dartmouth College Lebanon NH USA",
    "Laboratory of Genome Architecture and Dynamics The Rockefeller University New York NY USA",
    "Department of Biomedical Data Science Geisel School of Medicine at Dartmouth Lebanon NH USA",
    "Dartmouth Cancer Center Dartmouth Geisel School of Medicine Hanover NH USA",
    "Department of Biostatistics Dartmouth Geisel School of Medicine Lebanon NH USA",
    "Department of Pathology Medical College of Wisconsin Milwaukee WI USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Anneka L. Johnson Thomas"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Barbara Karakyriakou"
    },
    {
      "affs": [
        1
      ],
      "name": "Patricia C. Muskus"
    },
    {
      "affs": [
        0
      ],
      "name": "Alyssa M. Roberts"
    },
    {
      "affs": [
        3
      ],
      "name": "Justin Rendleman"
    },
    {
      "affs": [
        0
      ],
      "name": "Alexa Warren"
    },
    {
      "affs": [
        0
      ],
      "name": "Hanxu Lu"
    },
    {
      "affs": [
        1
      ],
      "name": "Kimberly A. Birmingham"
    },
    {
      "affs": [
        1
      ],
      "name": "Malone K. Friedman"
    },
    {
      "affs": [
        0
      ],
      "name": "Abigail E. Goen"
    },
    {
      "affs": [
        0
      ],
      "name": "Huijuan Yang"
    },
    {
      "affs": [
        4
      ],
      "name": "Owen M. Wilkins"
    },
    {
      "affs": [
        5
      ],
      "name": "Fred W. Kolling"
    },
    {
      "affs": [
        6
      ],
      "name": "Eugene Demidenko"
    },
    {
      "affs": [
        7
      ],
      "name": "Julie M. Jorns"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Brock C. Christensen"
    },
    {
      "affs": [
        0,
        1,
        7
      ],
      "name": "Todd W. Miller",
      "orcid": "0000-0001-8912-2909"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d5tykfkqk58nz.bib",
  "cited_by": 0,
  "doi": "10.1002/1878-0261.70307",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13398958/",
  "id": "d5tykfkqk58nz",
  "issns": [
    "1574-7891",
    "1878-0261"
  ],
  "landing_url": "https://doi.org/10.1002/1878-0261.70307",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Breast Cancer"
    ],
    [
      "heading",
      "Chromatin Structure and Remodeling"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1310|Estrogen and related hormone effects"
    ]
  ],
  "openalex": "W7169549455",
  "pdf_url": null,
  "pmcid": "PMC13398958",
  "pmid": "42464636",
  "published": "2026-07-17",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/d5tykfkqk58nz.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:23:27Z",
      "native_id": "PMC13398958",
      "source": "pmc",
      "url": "https://doi.org/10.1002/1878-0261.70307"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1310|Estrogen and related hormone effects",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "Pharmacological chromatin remodeling enhances response to estrogen therapy in ER + breast cancer",
  "title_text": "Pharmacological chromatin remodeling enhances response to estrogen therapy in ER + breast cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:20:55Z",
  "url": "https://research.draconitic.com/paper/d5tykfkqk58nz",
  "venue": "Molecular Oncology",
  "versions": []
}